The long-term overall goal of this Specialized Program of Translational Research in Acute Stroke SPOTRIAS) is to enhance and accelerate recovery of acute stroke patients by focused and innovative rapid nterventions for ischemic and hemorrhagic stroke. This will be achieved through the SPOTRIAS network as well as additional centers connected to the SPOTRIAS via the proposed projects. The Primary Specific Aims of this SPOTRIAS include three collaborative clinical studies, one translational pre-clinical study, and further development of four shared SPOTRIAS cores and the SPOTRIAS training program. Projects 1-3 are led by the UC SPOTRIAS Center. 1) Project 1: The Combination approach to Lysis utilizing Eptifibatide And rt-PA - Enhanced Regimen) or CLEARER Trial is a collaborative, multi-center, double-blind, randomized Phase II reperfusion trial of 100 subjects that tests the combination of 0.6 mg/kg of rt-PA and eptifibatide (a GP-llb/llla platelet receptor antagonist) administered within 3 hours of onset of ischemic stroke as compared to standard IV t-PA. 2) Project 2: The Spot Sign for Predicting and Treating Intracerebral Hemorrhage (ICH) Growth Study or STOP-IT Study is a collaborative multi-center phase-ll study of 184 subjects that examines the ability of contrast extravasation on CT angiography (CTA) to predict hematoma growth in patients with intracerebral hemorrhage and to explore the role CTA may play in treatment allocation using recombinant activated factor VII. 3) Project 3: Preclinical Models of Transcranial Ultrasound Thrombolysis (TRUST Study). TRUST will determine the optimal parameters for transcranial ultrasound thrombolysis in an in-vitro human clot model, and verify the safety of these optimized parameters as a therapy in an in-vivo rat ischemic stroke model. 4) Project 4: MR Rescue (NINDS/UCLA Lead Center). 5) Further development of four shared cores/databases for the SPOTRIAS network: a clinical patient database, a blood/tissue core, an imaging core, and a biostatistical/data management core. This includes the development of new projects that utilize these cores - such as a TIA proteomic study under development (UCSD Lead Center). 6) Continuation and further strengthening of the SPOTRIAS Training Program.